Cross-coupling reactions between two distinct nucleophilic partners have emerged as valuable transformations that display reactivity and selectivity orthogonal to classical metal-catalyzed couplings of electrophiles with nucleophiles. Oxidative coupling reactions often proceed under exceptionally mild conditions, employ base-metal mediators or catalysts, and in ideal cases, tolerate electrophilic functionality useful for subsequent transformations. The Cu-mediated union of aryl boronic acids and heteroatom nucleophiles exemplifies the power of such coupling manifolds. First reported by Chan and Lam, and Evans, functionalized aniline and phenol derivatives can be prepared from stable, readily available aryl boron species at room temperature by employing simple Cu-salts and mild organic bases. In addition to N- and O-based nucleophiles, sulfur, selenium, tellurium, and halogen nucleophiles are also suitable partners in these reactions. Despite the success of Chan-Evans-Lam type reactions in carbon-heteroatom bond construction processes, as well as an increasing appreciation for the mechanism of these transformations, a general method for the Cu-mediated arylation of stabilized sp3-carbon-based nucleophiles with organoboron reagents has not been established.
In the biosynthesis of polyketides and fatty acids, carbon-carbon bond formation proceeds via decarboxylative cross-condensation between malonic acid derivatives such as malonyl-CoA and enzyme-bound acyl electrophiles. A variety of conceptually related metal- or organocatalyzed reactions have been developed, in which malonates and related species undergo decarboxylation and coupling with carbonyl or allylic electrophiles. These reactions obviate the need for high temperatures, strongly basic mediators or prior stoichiometric manipulations to generate the enolate component. By contrast, there are limited reports of decarboxylative coupling reactions of malonate derivatives with aryl electrophiles.